4.5 Article Book Chapter

Clinical and Translational Implications of an Emerging Developmental Substructure for Autism

Journal

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-clinpsy-081219-110503

Keywords

development; causation; canalization; infancy; endophenotype; inheritance

Funding

  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intellectual and Developmental Disabilities Research Center at the Washington University School of Medicine in St. Louis) [P50 HD103525]
  2. UK Medical Research Council [MR/R011427/1, MR/T003057/1]
  3. Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) [777394]
  4. European Union's Horizon 2020 research and innovation program
  5. EFPIA (European Federation of Pharmaceutical Industries and Associations)
  6. Autism Speaks
  7. Autistica
  8. SFARI (Simon Foundation Autism Research Initiative)

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A significant portion of the population-attributable risk for autism is related to inherited polygenic risk. Recent studies suggest that inherited susceptibility may impact early developmental liabilities, predicting familial recurrence of the convergent syndrome of social communication disability that defines autism. This research points towards a novel developmental substructure for autism, with implications for understanding its neurobiological causes and informing future therapeutic approaches.
A vast share of the population-attributable risk for autism relates to inherited polygenic risk. A growing number of studies in the past five years have indicated that inherited susceptibility may operate through a finite number of early developmental liabilities that, in various permutations and combinations, jointly predict familial recurrence of the convergent syndrome of social communication disability that defines the condition. Here, we synthesize this body of research to derive evidence for a novel developmental substructure for autism, which has profound implications for ongoing discovery efforts to elucidate its neurobiological causes, and to inform future clinical and biomarker studies, early interventions, and personalized approaches to therapy.

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